The scan speed of microscope slide scanners in pathology has been increased to the point where the setup time required for configuring the scanner to acquire a scan is a significant portion of the total time, and especially when a large number (hundreds or even thousands) of slides must be scanned each day.
After one or more slides are prepared, they are visually examined by the technician and then loaded into a sample holder. The sample holder is then loaded into the slide scanner, or into the autoloader. Before high-resolution scanning, a preview image is recorded for all slides, usually using a camera in the scanner that is dedicated to this operation. The preview image may include only a single slide, or all of the slides in the tray. This preview image may contain an image of each slide's barcode as well as the area containing the specimen (usually tissue). The area containing the specimen is outlined to delimit the area that will be scanned. This can happen automatically or by the operator adjusting the size of the outline on the computer screen until it is near the edges of the sample. When the sample area is chosen automatically, before scanning the operator may check the image of each slide to ensure that the entire area of interest is included in the area to be scanned. Some scanners require focus points to be placed on the sample image before scanning, and that is done manually or automatically (and checked and possibly re-positioned by the operator) at this time. These focus points (or focus dots) are the positions on the sample where focus of the scanner will be measured for automatic adjustment of focus during scanning. In addition, a sub-area inside the region to be scanned with characteristics required for setting white balance (brightfield imaging) in the final scanned image may be chosen at this time. All other settings required to acquire the high-resolution scan are configured at this time with the help of the preview image.
For automated scanning, microscope slides are loaded automatically into a slide scanner. Two general types of microscope slide loaders are common. Slide loaders designed for loading slides onto standard microscopes (for example the Prior Scientific PL-100) and some slide loaders integrated into pathology scanners (for example Aperio ScanScope AT) place microscope slides onto the microscope stage or insert them into the optical path. A second type of slide loader handles sample holders (trays) containing one or more slides, with the advantage that the slides themselves are not handled during movement of the trays, and multiple slides can be loaded into a single tray. The size of slides that can be handled is limited only by the size of the tray and slide sizes can be mixed in a single run or even in a single tray.
When only a single slide, or slides in a single slide holder are to be imaged, the time required for acquiring preview images and subsequently setting up the high-resolution scan is only a few minutes, however when hundreds of slides must be scanned, this pre-scan preparation time becomes significantly larger, and since the scanning system is used for this pre-scan preparation procedure, this limits the number of slides that can be scanned per day.
One example of a commonly-used workflow is described in FIG. 1. The sequence of operations performed in the scanner before scanning commences is as follows:
1. Insert separate slides (or sample holders) 101 into the scanner 100 or into the scanner's autoloader.
2. Using the scanner, acquire preview images of each slide 102. A single image showing all of the slides in the sample holder or separate images of each slide may be used.
3. Using the preview image (or part of the preview image) of each slide in the sample holder, perform automated or manual scan setup 103 for the high-resolution scan. This automated or manual scan setup includes some or all of the following steps for each separate slide, or for each slide in the sample holder:
Find the area of the slide containing tissue to be scanned.
Place focus dots on the sample image inside the area to be scanned.
Choose a location for setting white balance in the final scanned image.
Choose locations for measuring sample tilt inside the area to be scanned.
Read barcode on each slide and on the sample holder to record data required to set imaging parameters (e.g. which stain is on the tissue, whether the slide should be read in brightfield or fluorescence, etc.).
1. Review some or all of the items in Step 3 above (optional). The scanner now knows where all of the microscope slides are in its slide store, and scan priority for a particular slide can be changed by the operator at this time.
2. Start Scanning 104 to image the Region of Interest (ROI) identified in the preview image. Note that the scanner itself has been used during steps 2-4 and has been unavailable for scanning during this time.
The drawbacks of this commonly-used workflow include, but are not limited to:
1. Slide scanning is a sequential process of acquiring preview images, creating scan setups, and scanning high-resolution images.
2. The Scanner cannot acquire high-resolution images while preview images are being captured by the scanning system.
3. The Scanner cannot acquire high-resolution images while scan-setup is taking place.
4. Preview images cannot be taken while scan-setup information is being generated.
5. Preview images cannot be acquired while high resolution images are being captured.
6. Scan-setup cannot take place while preview images are being captured.
7. Scan-setup cannot take place while high resolution images are being captured.
8. The scanner may not be able to acquire high resolution images while barcode and label are being captured.
9. Samples loaded into the scanner (or the scanner's autoloader) while the scanner is in operation are not identified until after the scanner completes reading each sample's barcode during the preview scan process, so scanning of critical samples must wait until the scanner collects a preview image of that sample and interrupts the scanning process to scan that important sample.Definitions:
For the purposes of this disclosure “Low Resolution” may be defined as spatial resolution greater than 0.5 micron.
For the purposes of this disclosure “High Resolution:” may be defined as spatial resolution less than or equal to 0.5 micron.
For the purposes of this disclosure, “Preview Image” may be defined as a low resolution overview image of a partial, whole or many specimen(s) used to setup the required parameters for performing a high-resolution scan. It can also include an image of labels, bar codes, and other identifiers of the slide, sample holder, and specimen.
For the purposes of this disclosure “Sample” may be defined as anything presented to the instrument for the purpose of being imaged, generally a specimen on a microscope slide, the entire microscope slide containing the specimen, a microwell plate, a semiconductor wafer, etc, that can be inserted into the scanner/autoloader for imaging.
For the purposes of this disclosure “Sample Holder” may be defined as any device that can be used to hold one or more samples, and can be inserted into the scanner/autoloader for imaging.
For the purposes of this disclosure “Autoloader” may be defined as a device that loads samples or sample holders into the scanner.
For the purposes of this disclosure “Workstation” may be defined as a computer to control the scanner and/or autoloader and can generate scan-control information from preview images (scan-setup).
For the purposes of the disclosure “Scan-Setup” may be defined as a process that uses a preview image to generate all of the information required by the scanner for scanning a high-resolution image of a specified area. This information can include but is not limited to information defining the region of interest, focus positions, flat fielding, colour content, specimen type identification, corresponding scanning protocol, etc.
For the purposes of this disclosure “Preview Imager” may be defined as a device dedicated to capturing preview images. In some cases the Preview Imager will also have the capability to generate scan-setup information from the preview images. A preview imager can be an independent device or a part of a larger system, for example, part of the scanner and/or autoloader.
For the purposes of this disclosure “ROI” (region of interest) may be defined as the area of the specimen that will be imaged at high resolution.
For the purposes of this disclosure “Tablet” may be defined as a general-purpose computer contained in a single panel. Its distinguishing characteristic is the use of a touch screen as one of several input devices.